安进（Amgen）公司于 6月13日披露，美国FDA已批准其Xgeva（denosumab，狄诺塞麦）扩大用于治疗成人和某些青少年的骨巨细胞瘤（GCTB），这使它成为成为在美国对付该罕见病的首个药物。FDA药物评价研究中心血液学和肿瘤学产品办公室主任Richard Pazdur说：“该药通过该机构的优先审查程序审查，它将为不能进行手术，或否则必须接受广泛、影响生活的手术的患者提供一种急需的治疗选择。”
这一扩大用途批准的基础是从一对临床试验的数据。总共招募了305名成人和青少年GCTB患者，他们抑或是复发的，抑或是不适合手术切除者。FDA称：这187名患者经肿瘤测量，平均3个月后观察到47名肿瘤缩小，51％患者有客观应答，持续至少8个月。数据还显示，平均随访20个月过程中有3名瘤体缩小的患者GCTB重新生长。
安进公司表示：该药对GCTB患者的安全性“与先前骨转移患者的研究报告类似，并在骨骼发育成熟的青少年和成人中情况相似。”因为Xgeva是一种靶向作用于RANKL的单克隆抗体，可能会伤害胎儿，FDA告诫有生育能力的妇女采取“高度有效的避孕手段”。
Xgeva最早于2010年在美国获得批准，用于实体瘤骨转移成人防止骨骼相关事件，2011年在欧洲也获准用于同一适应症。
Indication
XGEVA® (denosumab) is indicated for the prevention of skeletal-related events in patients with bone metastases from solid tumors.
XGEVA® is not indicated for the prevention of skeletal-related events in patients with multiple myeloma.
Important Safety Information
Hypocalcemia
Pre-existing hypocalcemia must be corrected prior to initiating therapy with XGEVA®(denosumab). XGEVA® can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Monitor levels more frequently when XGEVA® is administered with other drugs that can also lower calcium levels. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
An increased risk of hypocalcemia has been observed in clinical trials of patients with increasing renal dysfunction, most commonly with severe dysfunction (creatinine clearance less than 30 mL/minute and/or on dialysis), and with inadequate/no calcium supplementation. Monitor calcium levels and calcium and vitamin D intake.
Hypersensitivity
XGEVA® (denosumab) is contraindicated in patients with known clinically significant hypersensitivity to XGEVA®, including anaphylaxis that has been reported with use of XGEVA®. Reactions may include hypotension, dyspnea, upper airway edema, lip swelling, rash, pruritus, and urticaria. If an anaphylactic or other clinically significant allergic reaction occurs, initiate appropriate therapy and discontinue XGEVA® therapy permanently.
Drug Products with Same Active Ingredient
Patients receiving XGEVA® (denosumab) should not take Prolia® (denosumab).
Osteonecrosis of the Jaw
Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA® (denosumab), manifesting as jaw pain, osteomyelitis, osteitis, bone erosion, tooth or periodontal infection, toothache, gingival ulceration, or gingival erosion. Persistent pain or slow healing of the mouth or jaw after dental surgery may also be manifestations of ONJ. In clinical trials in patients with osseous metastasis, the incidence of ONJ was higher with longer duration of exposure.
Perform an oral examination and appropriate preventive dentistry prior to the initiation of XGEVA® and periodically during XGEVA® therapy. Advise patients regarding oral hygiene practices. Avoid invasive dental procedures during treatment with XGEVA®.
Patients who are suspected of having or who develop ONJ while on XGEVA® should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral Fracture
Atypical femoral fracture has been reported with XGEVA® (denosumab). These fractures can occur anywhere in the femoral shaft from just below the lesser trochanter to above the supracondylar flare and are transverse or short oblique in orientation without evidence of comminution.
Atypical femoral fractures most commonly occur with minimal or no trauma to the affected area. They may be bilateral and many patients report prodromal pain in the affected area, usually presenting as dull, aching thigh pain, weeks to months before a complete fracture occurs. A number of reports note that patients were also receiving treatment with glucocorticoids (e.g. prednisone) at the time of fracture. During XGEVA® treatment, patients should be advised to report new or unusual thigh, hip, or groin pain. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be eva luated to rule out an incomplete femur fracture. Patient presenting with an atypical femur fracture should also be assessed for symptoms and signs of fracture in the contralateral limb. Interruption of XGEVA® therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Embryo-Fetal Toxicity
XGEVA® (denosumab) can cause fetal harm when administered to a pregnant woman. Based on findings in animals, XGEVA® is expected to result in adverse reproductive effects.
Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after the last dose of XGEVA®. Apprise the patient of the potential hazard to a fetus if XGEVA® is used during pregnancy or if the patient becomes pregnant while patients are exposed to XGEVA®.
Adverse Reactions
The most common adverse reactions in patients receiving XGEVA® (denosumab) with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea. The most common adverse reactions resulting in discontinuation were osteonecrosis and hypocalcemia.